ABSTRACT
Prorocentroic acid (PA) was isolated from the dinoflagellate Prorocentrum hoffmannianum. Relative configurations for its 35 asymmetric centers were determined by analysis of NMR data including heteronuclear couplings and quantum mechanical calculations. PA was tested by using murine cortical neurons grown on microelectrode arrays. Long-term exposure to subtoxic concentrations induced a significant reorganization of neuronal signaling, mainly by changes in the bursting activity. The observed effects could be due to the activation of a plasticity process.
Subject(s)
Acids/chemistry , Carbon/chemistry , Dinoflagellida/chemistry , Animals , Magnetic Resonance Spectroscopy , Mice , Molecular Structure , Organic ChemicalsABSTRACT
Belizentrin (1), a novel 25-membered polyketide-derived macrocycle, was isolated from cultures of the marine dinoflagellate Prorocentrum belizeanum. This metabolite is the first member of an unprecedented class of polyunsaturated and polyhydroxylated macrolactams. The structure of 1 was primarily determined by NMR and computational methods. Pharmacological assays with cerebellar cells showed that 1 produces important changes in neuronal network integrity at nanomolar concentrations.
Subject(s)
Dinoflagellida/chemistry , Lactams, Macrocyclic/isolation & purification , Lactams, Macrocyclic/chemistry , Lactams, Macrocyclic/pharmacology , Marine Biology , Molecular Structure , Neurons/drug effects , Nuclear Magnetic Resonance, BiomolecularABSTRACT
Marine organisms are an increasingly important source of novel metabolites, some of which have already inspired or become new drugs. In addition, many of these molecules show a high degree of novelty from a structural and/or pharmacological point of view. Structure determination is generally achieved by the use of a variety of spectroscopic methods, among which NMR (nuclear magnetic resonance) plays a major role and determination of the stereochemical relationships within every new molecule is generally the most challenging part in structural determination. In this communication, we have chosen okadaic acid as a model compound to perform a computational chemistry study to predict 1H and 13C NMR chemical shifts. The effect of two different solvents and conformation on the ability of DFT (density functional theory) calculations to predict the correct stereoisomer has been studied.
Subject(s)
Biological Products/chemistry , Okadaic Acid/chemistry , Algorithms , Animals , Computational Biology , Crystallography, X-Ray , Dinoflagellida , Magnetic Resonance Spectroscopy , Models, Molecular , Molecular Conformation , Quantum Theory , Solvents , StereoisomerismABSTRACT
Adriatoxin-B (ATX-B) is the first C(13) terminal truncated YTX analogous metabolite that was isolated from large-scale cultures of the dinoflagellate Protoceratium reticulatum. The structure and conformational behavior of ATX-B was elucidated by a combination of NMR spectroscopy experiments and a conformational analysis. The isolation of this metabolite, which possesses a clear structural relationship with adriatoxin, supports the idea that the real source of these cut down substances is in the microalgae and not in the mollusks, via metabolic degradation like it has been assumed until now.
Subject(s)
Dinoflagellida/physiology , Marine Toxins/chemistry , Oxocins/chemistry , Pyrans/chemistry , Animals , Chromatography, High Pressure Liquid , Magnetic Resonance Spectroscopy , Marine Toxins/metabolism , Mollusk Venoms , Oxocins/metabolism , Pyrans/metabolism , Solid Phase Extraction , Spectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationABSTRACT
Diarrhetic Shellfish Poisoning (DSP) is a specific type of food poisoning, characterized by severe gastrointestinal illness due to the ingestion of filter feeding bivalves contaminated with a specific suite of toxins. It is known that the problem is worldwide and three chemically different groups of toxins have been historically associated with DSP syndrome: okadaic acid (OA) and dinophysistoxins (DTXs), pectenotoxins (PTXs) and yessotoxins (YTXs). PTXs and YTXs have been considered as DSP toxins because they can be detected with the bioassays used for the toxins of the okadaic acid group, but diarrhegenic effects have only been proven for OA and DTXs. Whereas, some PTXs causes liver necrosis and YTXs damages cardiac muscle after intraperitoneal injection into mice. On the other hand, azaspiracids (AZAs) have never been included in the DSP group, but they cause diarrhoea in humans. This review summarizes the origin, characterization, structure, activity, mechanism of action, clinical symptoms, method for analysis, potential risk, regulation and perspectives of DSP and associated toxins produced by marine dinoflagellates.
